European regulators say they expanded an investigation started earlier this month into the risk of suicidal thoughts among patients taking GLP-1 receptor agonists, including Novo Nordisk‘s popular weight loss and diabetes drugs, to include more medications in the class.

After receiving reports from Icelandic health officials about three cases of suicidal thoughts and self-injury in patients taking Ozempic and Saxenda, the European Medicines Agency (EMA) began looking into whether there’s a connection between the incidents and the active ingredients in the medicines – semaglutide and liraglutide.

Since launching the probe July 3, the EMA’s safety committee has uncovered 150 more adverse event reports, prompting the agency to broaden the scope of the review to include other GLP-1 treatments, according to a July 11 announcement. 

In a statement, the EMA stressed that it is “not yet clear whether the reported cases are linked to the patients’ underlying conditions or other factors,” but noted that the medications “are widely used,” with an exposure of more than 20 million patients annually. Additionally, suicidal behavior is not listed as a side effect in the EU product information for any GLP-1 receptor agonists.

According to the EMA, the investigation is expected to wrap up in November.

In 2014, Novo Nordisk’s Saxenda, which contains liraglutide, became the first medication of its kind to be approved for weight loss in people without diabetes.

Authorized by the U.S. Food and Drug Administration in 2017, Ozempic is a self-injectable treatment made using semaglutide for adults with Type 2 diabetes that works by mimicking a natural hormone the body releases when a person eats, potentially causing weight loss as a secondary effect.

Wegovy, which also contains semaglutide, was approved in 2021 specifically for chronic weight management in individuals who are obese or overweight with at least one weight-related condition. About six months after it hit the market, Novo Nordisk announced the drug was in short supply, prompting many physicians to shift to off-label prescriptions for semaglutide diabetes drugs Ozempic and Rybelsus for patients who needed or wanted to lose weight but could not access Wegovy.

This trend only intensified under the influence of social media campaigns and celebrities promoting semaglutide, eventually leading to ongoing shortages that the company is still working to resolve.

In a July 13 statement to NJBIZ, Novo Nordisk – which has its U.S. headquarters in Plainsboro – said it “remains confident in the benefit risk profile of the products and remains committed to ensuring patient safety.”

“We take all reports about adverse events from use of our medicines very seriously. GLP-1 receptor agonists have been used to treat type 2 diabetes for more than 15 years and for treatment of obesity for eight years,” the company said.

Novo Nordisk also pointed to safety data collected during large clinical trial programs and post marketing surveillance that showed “no casual association between semaglutide or liraglutide and suicidal and self-harming thoughts.”

In the U.S., prescribing information for Saxenda does not list suicidal thoughts or self-injury as side effects. But, it does include a recommendation to monitor patients for depression or suicidal thoughts and to discontinue the drug if symptoms develop.

The prescribing information for Wegovy in the U.S. notes that suicidal ideation and behavior has been reported in clinical trials for other weight management products and says that patients on Wegovy should be monitored for depression and suicidal thoughts or behavior.

“In the U.S., FDA requires medications for chronic weight management that work on the central nervous system, including Wegovy and Saxenda, to carry a warning about suicidal behavior and ideation. This event had been reported in clinical trials with other weight management products,” the company said. “Novo Nordisk is continuously performing surveillance of the data from ongoing clinical trials and real-world use of its products and collaborates closely with the authorities to ensure patient safety and adequate information to health care professionals.”

The EMA’s announcement comes a little more than a month since the FDA warned about the safety risks of using unauthorized versions of these drugs, saying it has received reports of adverse health reactions related to modified, or “compounded,” variations that are gaining popularity with consumers amid the continuing shortage of Ozempic and Wegovy.

As the sole patent holder of semaglutide, Novo Nordisk filed lawsuits against several medical spas, weight loss clinics and compounding pharmacies for allegedly selling unauthorized versions of the drugs.